We have developed a surgical method of manipulating feline peripheral nerve regeneration to separate spatially the temporal sequence of events of axon/Schwann cell interaction during nerve fiber formation. The method allows regenerating axons from the peroneal nerve to reinnervate the distal stump of an axon- and myelin-free, Schwann-cell enriched, chronically denervated tibial nerve distal stump. Three zones can be morphologically delineated in the tibial nerve stump after three weeks of reinnervation: (a) a proximal myelinated zone, (b) a more distal, non-myelinated axon-Schwann cell contact zone, and (c) a distal axon-free Schwann cell non-contact zone. This model is being employed to study the control of Schwann behavior during nerve degeneration and regeneration, with special emphasis on the regulation of myelination. Studies completed to date have demonstrated: (a) Schwann cells undergo division shortly after loss of the axolemma during Wallerian degeneration following nerve transection, (b) the resulting population of axon-free Schwann cells does not manufacture detectable levels of myelin protein, (c) Schwann cell undergo a second wave of division when presented with axons during regeneration and prior to myelination, (d) the resulting population of axon-associated Schwann cells commence myelinogenesis; synthesis of proteins comigrating with P1 and P2 is expressed prior to synthesis of P0 glycoprotein, and (e) Schwann-cell myelin-protein synthesis commences prior to the appearance of myelin lamellae. These studies demonstrate that axons regulate the behavior of Schwann cells with respect to control of Schwann-cell division and myelination. Control is probably exerted at the level of the cell membrane.